The proposed series of experiments are designed to describe the earliest period of ontogenetic development of central monoaminergic neurons by use of peroxidase and degeneration staining procedures - the latter being used after selective neurotoxins. The overriding theme of the proposal is a description of the mechanisms associated with formation of axonal sprouts in developing or regenerating neurons. To determine the importance of axonal damage on collateral fiber sprouting, lesions will be made of the dorsal adrenergic bundle and various means, including application of nerve growth factors into the lesion site, will be used to initiate or accelerate sprouting in the collateral branch of the locus coeruleus to the cerebellum. Chemical lesioning in prenates will be used in an attempt to initiate mechanisms associated with sprouting of central serotonergic neurons. Transplantations of developing monoaminergic nuclei to different regions of a recipient brain will be used for the most detailed study on determination of the factors associated with sprouting, because of the advantage that this system offers for isolation of variables. The consistent production of noradrenergic fiber sprouting in the cerebellum, following 6-hydroxydopa treatment of neonates provides a means for initiation of sprouting and thereby the means to study the mechanisms involved in such a process. It is expected that the proposed series of studies will lead to a better understanding of how mature and immature damaged neurons in the CNS can be stimulated to regenerate/sprout.